An Update on the Nitrogen Heterocycle Compositions and Properties of U.S. FDA-Approved Pharmaceuticals (2013-2023).

This Perspective is a continuation of our analysis of U.S. FDA-approved small-molecule drugs (1938-2012) containing nitrogen heterocycles. In this study we report drug structure and property analyses of 321 unique new small-molecule drugs approved from January 2013 to December 2023 as well as information about frequency of important heteroatoms such as sulfur and fluorine and key small nitrogen substituents (CN and NO2). The most notable change is an incredible increase in drugs containing at least one nitrogen heterocycle─82%, compared to 59% from preceding decades─as well as a significant increase in the number of nitrogen heterocycles per drug. Pyridine has claimed the #1 high-frequency nitrogen heterocycle occurrence spot from piperidine (#2), with pyrimidine (#5), pyrazole (#6), and morpholine (#9) being the big top 10 climbers. Also notable is high number of fused nitrogen heterocycles, apparently driven largely by newly approved cancer drugs.

A Structural Analysis of the FDA Green Book-Approved Veterinary Drugs and Roles in Human Medicine.

The FDA Green Book is a list of all drug products that have been approved by the FDA for use in veterinary medicine. The Green Book, as published, lacks structural information corresponding to approved drugs. To address this gap, we have compiled the structural data for all FDA Green Book drugs approved through the end of 2019. Herein we discuss the relevance of this data set to human drugs in the context of structural classes and physicochemical properties. Analysis reveals that physicochemical properties are highly optimized and consistent with a high probability of favorable drug metabolism and pharmacokinetic properties, including good oral bioavailability for most compounds. We provide a detailed analysis of this data set organized on the basis of structure and function. Slightly over half (51%) of vet drugs are also approved in human medicine. Combination drugs are biologics are also discussed.

Body Condition Scoring for Adult Zebrafish (Danio rerio).

Body condition scoring (BCS) is a simple, rapid, noninvasive tool used to assess body condition in animals. In this study, wedeveloped and validated a diagram-based BCS for adult zebrafish (Danio rerio), a popular research model. After receiving 20min of hands-on training regarding the scoring system, 5 people each rated 95 adult zebrafish. The fish then were euthanizedand measured to establish body condition indices (BMI and the Fulton K factor). Both condition indices were highly correlatedwith fish width. Using correlation data and observed trends in fish width, we established expected BCS definitions. Wevalidated the BCS definitions in 2 ways. First, we calculated the Pearson correlation coefficient between the average observedBCS and expected BCS; this statistic revealed very strong correlation between observed and expected BCS. In addition, weassessed the predictive power of BCS by using multinomial logistic regression and then applied the fitted model to evaluatethe accuracy of the predictions (BCS compared with BMI, 85%; BCS compared with K factor, 61%). Finally, to determine therobustness of BCS to variation among raters, we calculated the intraclass correlation coefficient and demonstrated high interrater reliability. In conclusion, adult zebrafish BCS can be used to quickly identify animals with different body conditionindices (thin to obese). In addition, the diagram-based chart is easy to use and implement accurately, with minimal training.